Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical

Susan Wang, Jin Luo, Douglas A. Lantrip, David J. Waters, Carla J. Mathias, Mark Green, Philip L. Fuchs, Philip S. Low

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

Folate-conjugated metal chelates have been proposed as potential imaging agents for cancers that overexpress folate receptors. In a previous study, folic acid was linked through its γ-carboxyl group to deferoxamine (DF), and the 67Ga-labeled complex ([67Ga]DF-folate) was examined for in vivo tumor targeting efficiency in athymic mice with a human tumor cell implant. Although superb tumor-to background contrast was obtained, slow hepatobiliary clearance would compromise imaging of abdominal tumors such as ovarian cancer. In the present study, folic acid was conjugated to an alternative chelator, diethylenetriaminepentaacetic acid (DTPA), via an ethylenediamine spacer. The desired DTPA-folate(γ) regioisomer was synthesized by two different approaches, purified by reversed phase column chromatography, and characterized mainly by analytical HPLC, mass spectroscopy, and NMR. In cultured tumor cells, uptake of [111In]DTPA-folato(γ) was found to be specific for folate receptor-bearing cells, and the kinetics of uptake were similar to those of free folate and other folate-conjugated molecules. In the normal rat, intravenously administered [111In]DTPA-folate(γ) was found to be rapidly excreted into the urine, giving intestinal levels of radiotracer 10-fold lower than those observed with [67Ga]DF-folate(γ) at 4 h. In a preliminary mouse imaging study, a folate receptor-positive KB cell tumor was readily visualized by γ scintigraphy 1 h following intravenous administration of [111In]DTPA-folate(γ).

Original languageEnglish (US)
Pages (from-to)673-679
Number of pages7
JournalBioconjugate Chemistry
Volume8
Issue number5
DOIs
StatePublished - Sep 1997
Externally publishedYes

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Radiopharmaceuticals
Folic Acid
Tumors
Acids
Neoplasms
Deferoxamine
Imaging techniques
ethylenediamine
Bearings (structural)
Cells
Column chromatography
DTPA folate
Cultured Tumor Cells
KB Cells
Rats
Reverse-Phase Chromatography
Nuclear magnetic resonance
Chelating Agents
Spectroscopy
Nude Mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Clinical Biochemistry
  • Chemistry(all)
  • Organic Chemistry

Cite this

Wang, S., Luo, J., Lantrip, D. A., Waters, D. J., Mathias, C. J., Green, M., ... Low, P. S. (1997). Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical. Bioconjugate Chemistry, 8(5), 673-679. https://doi.org/10.1021/bc9701297

Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical. / Wang, Susan; Luo, Jin; Lantrip, Douglas A.; Waters, David J.; Mathias, Carla J.; Green, Mark; Fuchs, Philip L.; Low, Philip S.

In: Bioconjugate Chemistry, Vol. 8, No. 5, 09.1997, p. 673-679.

Research output: Contribution to journalArticle

Wang, S, Luo, J, Lantrip, DA, Waters, DJ, Mathias, CJ, Green, M, Fuchs, PL & Low, PS 1997, 'Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical', Bioconjugate Chemistry, vol. 8, no. 5, pp. 673-679. https://doi.org/10.1021/bc9701297
Wang, Susan ; Luo, Jin ; Lantrip, Douglas A. ; Waters, David J. ; Mathias, Carla J. ; Green, Mark ; Fuchs, Philip L. ; Low, Philip S. / Design and synthesis of [111In]DTPA-folate for use as a tumor-targeted radiopharmaceutical. In: Bioconjugate Chemistry. 1997 ; Vol. 8, No. 5. pp. 673-679.
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